DESCRIPTION: (Applicant's Description) The overall objective of this project is to continue to further escalate tumor doses and maximize normal tissue sparing in patients treated with radiation therapy for cancer. A main hypothesis of this work is that a higher tumor dose will help improve local tumor control, and that improved sparing of normal tissue will improve the quality of life for surviving patients. In the previous program project, we began a number of clinical studies addressing this hypothesis, and many of these studies continue in the currently proposed research. These studies include dose escalation trials (in lung, brain, prostate and liver cancer) and normal tissue sparing studies (in head and neck cancer). To date, these studies have shown that conformal radiation using 3-dimensional planning and delivery tools enabled the safe escalation of tumor dose in each site and have also shown improved sparing of normal tissue compared to that typical of standard radiation techniques. The studies and clinical protocols proposed here will continue to further push these limits with the utilization of continuing improvements in the planning and delivery process (e.g., more sophisticated IMRT, improved handling of organ motion and setup uncertainties, generalized optimization of the planning/delivery process) provided by the other projects in the program project. For each clinical protocol, the aim is to determine the maximally tolerated dose that can be delivered safely. In addition, the data gathered through these studies will allow quantitative analysis and modeling of dose-volume-effect relationships which will help guide future treatment strategies. Phase II trials will be conducted for patients with glioblastoma, lung cancer, and intrahepatic cancer. The results of the studies proposed in this project will lead toward development of Phase III studies to assess accurately the effect of high dose conformal therapy on patient outcome.